Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003461885 | SCV004196280 | uncertain significance | Lynch syndrome 1 | 2023-08-31 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004011326 | SCV004833341 | uncertain significance | Lynch syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 476 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV004364782 | SCV005033217 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing | The p.P476R variant (also known as c.1427C>G), located in coding exon 9 of the MSH2 gene, results from a C to G substitution at nucleotide position 1427. The proline at codon 476 is replaced by arginine, an amino acid with dissimilar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 Jan;108:163-175). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |